四川地区HIV感染患者合并分枝杆菌感染特征与耐药性分析
|
摘要
目的分析四川地区人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者合并分枝杆菌感染与耐药情况,丰富本地区相关的流行病学资料。方法选择2014年1月-2017年6月于医院就诊的HIV感染者疑似同时合并分枝杆菌感染患者的各类标本(3 078例)进行分离培养,阳性标本采用噻吩-2-羧酸肼(TCH)和对硝基苯甲酸(PNB)鉴别培养基进行菌型鉴定及药物敏感性试验,非结核分枝杆菌(Non-tuberculous Mycobacterium,NTM)采用基因芯片或16SrDNA基因测序法进行种群鉴定。结果共收集到HIV感染疑似合并分枝杆菌感染患者标本3 078份,分离出阳性菌株458株,阳性率为14.88%。去除重复菌株菌后,共得到369株非重复性分枝杆菌,其中结核分枝杆菌(MTB)313株,非结核分枝杆菌(NTM)56株。2016年和2017 HIV合并NTM的感染率增加较明显,56株NTM有21株进行了种群鉴定,得到鸟分枝杆菌8株,龟或脓肿分枝杆菌6株,堪萨斯分枝杆菌5株,胞内分枝杆菌2株。313株MTB中有86株至少对一种抗结核药物耐药,耐多药(MDR)37株,广泛耐药(XDR)7株;313株MTB对异烟肼(INH)、利福平(RFP)、链霉素(SM)、氧氟沙星(OFX)、阿米卡星(AMK)、卡那霉素(KM)、乙胺丁醇(EMB)和卷曲霉素(CPM)耐药率分别为20.13%、13.74%、12.14%、10.22%、1.92%、1.92%、1.28%和1.28%,单耐药以单耐INH和单耐OFX为主。不同种类NTM对8种抗结核药物均呈现高度耐药,全部NTM均对INH耐药,较少NTM(除堪萨斯分枝杆菌外)对EMB耐药,较少NTM对CPM和AMK耐药。结论四川地区HIV感染者合并分枝杆菌感染以MTB为主,HIV合并MTB感染者与普通结核患者相比耐药风险未增加,但OFX耐药率较高,要警惕喹诺酮类药物滥用。四川地区HIV合并NTM感染以鸟分枝杆菌较为常见,EMB、CPM和AMK对NTM的效果较好。
OBJECTIVE To investigate the distribution and drug resistance of Mycobacterium infection in patients infected with HIV in Sichuan, so as to enrich the relevant epidemiological data in this areas. METHODS Various specimens(3 078 cases) of HIV-infected patients with suspected Mycobacterium infection treated in the hospital from Jan. 2014 to Jun. 2017 were subjected to bacteria isolation and culture, The positive specimens were treated with identification medium and non-Mycobacterium tuberculosis(non-tuberculous,ntm) Gene chip or 16 SrDNA gene sequencing method was used for population identification.The positive strains were identified by thiophene-2-carboxylic acid hydrazine(TCH) and P-aminobenzoic acid(PNB) identification medium for bacterial identification and drug sensitivity test. For non-tuberculosis Mycobacterium(NTM), population identification was conducted using gene chip or 16 SrDNA gene sequencing. RESULTS A total of 3078 samples of HIV-infected patients with suspected Mycobacterium infection were collected, from which 458 positive strains were isolated, and the positive rate was 14.88%. After removing the repetitive strains, 369 non-repetitive Mycobacterium strains were obtained, including 313 strains of Mycobacterium tuberculosis(MTB) and 56 strains of non-tuberculosis Mycobacterium(NTM). In 2016 and 2017, the infection rate of HIV-infected patients with NTM increased significantly. Twenty-one out of the 56 NTM strains were identified. Eight strains of Mycobacterium avium, six strains of Mycobacterium turtle or Mycobacterium abscess, five strains of Mycobacterium Kansas and two strains of intracellular Mycobacterium were obtained. Among the 313 MTBs, 86 were resistant to at least one antituberculosis drug, 7 were multidrug resistant(MDR) and 37 were extensively resistant(XDR). The resistance rates of the 313 MTBs to isoniazid(INH), rifampicin(RFP), streptomycin(SM), ofloxacin(OFX), amikacin(AMK), kanamycin(KM), ethambutol(EMB) and capreomycin(CPM) were 20.13%, 13.74%, 12.14%, 12.14%. 10.22%, 1.92%, 1.92%, 1.28% and 1.28%, respectively. Single drug resistance was mainly found with INH and OFX. Different kinds of NTM all showed high resistance to 8 kinds of anti-tuberculosis drugs. All NTM strains were resistant to INH, fewer NTM strains(except Mycobacterium Kansas) were resistant to EMB, and even fewer NTM strains were resistant to CPM and AMK. CONCLUSION The prevalence of HIV complicated with Mycobacterium infection in Sichuan area was dominated by MTB. There was no significant difference in the rate of drug resistance among HIV patients with MTB infection and tuberculosis patients. However, the OFX drug resistance rate was high, so it is necessary to guard against quinolone abuse. Mycobacterium avium was the main cause of NTM infection in HIV patients in Sichuan area. EMB, CPM and AMK had relatively good clinical effect on NTM.
OBJECTIVE To investigate the distribution and drug resistance of Mycobacterium infection in patients infected with HIV in Sichuan, so as to enrich the relevant epidemiological data in this areas. METHODS Various specimens(3 078 cases) of HIV-infected patients with suspected Mycobacterium infection treated in the hospital from Jan. 2014 to Jun. 2017 were subjected to bacteria isolation and culture, The positive specimens were treated with identification medium and non-Mycobacterium tuberculosis(non-tuberculous,ntm) Gene chip or 16 SrDNA gene sequencing method was used for population identification.The positive strains were identified by thiophene-2-carboxylic acid hydrazine(TCH) and P-aminobenzoic acid(PNB) identification medium for bacterial identification and drug sensitivity test. For non-tuberculosis Mycobacterium(NTM), population identification was conducted using gene chip or 16 SrDNA gene sequencing. RESULTS A total of 3078 samples of HIV-infected patients with suspected Mycobacterium infection were collected, from which 458 positive strains were isolated, and the positive rate was 14.88%. After removing the repetitive strains, 369 non-repetitive Mycobacterium strains were obtained, including 313 strains of Mycobacterium tuberculosis(MTB) and 56 strains of non-tuberculosis Mycobacterium(NTM). In 2016 and 2017, the infection rate of HIV-infected patients with NTM increased significantly. Twenty-one out of the 56 NTM strains were identified. Eight strains of Mycobacterium avium, six strains of Mycobacterium turtle or Mycobacterium abscess, five strains of Mycobacterium Kansas and two strains of intracellular Mycobacterium were obtained. Among the 313 MTBs, 86 were resistant to at least one antituberculosis drug, 7 were multidrug resistant(MDR) and 37 were extensively resistant(XDR). The resistance rates of the 313 MTBs to isoniazid(INH), rifampicin(RFP), streptomycin(SM), ofloxacin(OFX), amikacin(AMK), kanamycin(KM), ethambutol(EMB) and capreomycin(CPM) were 20.13%, 13.74%, 12.14%, 12.14%. 10.22%, 1.92%, 1.92%, 1.28% and 1.28%, respectively. Single drug resistance was mainly found with INH and OFX. Different kinds of NTM all showed high resistance to 8 kinds of anti-tuberculosis drugs. All NTM strains were resistant to INH, fewer NTM strains(except Mycobacterium Kansas) were resistant to EMB, and even fewer NTM strains were resistant to CPM and AMK. CONCLUSION The prevalence of HIV complicated with Mycobacterium infection in Sichuan area was dominated by MTB. There was no significant difference in the rate of drug resistance among HIV patients with MTB infection and tuberculosis patients. However, the OFX drug resistance rate was high, so it is necessary to guard against quinolone abuse. Mycobacterium avium was the main cause of NTM infection in HIV patients in Sichuan area. EMB, CPM and AMK had relatively good clinical effect on NTM.
引文
[1] Barnett D,Walker B,Landay A,et al.CD4 immunophenotyping in HIV infection[J].Nat Rev Microbiol,2008,6(11 Suppl):S7-15.
[2] Day JH,Grant AD,Fielding KL,et al.Does tuberculosis increase HIV load?[J].J Infect Dis,2004,190(9):1677-1684.
[3] Lawn SD,Badri M,Wood R.Tuberculosis among HIV-infected patients receiving HAART:long term incidence and risk factors in a South African cohort[J].AIDS,2005,19(18):2109-2116.
[4] Lopez-Gatell H,Cole SR,Margolick JB,et al.Effect of tuberculosis on the survival of HIV-infected men in a country with low tuberculosis incidence [J].AIDS,2008,22(14):1869-1873.
[5] The American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC).Targeted tuberculin testing and treatment of latent tuberculosis infection [J].MMWR Recomm Rep,2000,49(RR-6):1-51.
[6] Horsburgh CR Jr.Priorities for the treatment of latent tuberculosis infection in the United States[J].N Engl J Med,2004,350(20):2060-2067.
[7] Atwal SS,Puranik S,Madhav RK,et al.High resolution computed tomography lung spectrum in symptomatic adult HIV-positive patients in South-East Asian nation [J].J Clin Diagn Res,2014,8(6):RC12-RC16.
[8] Centers for Disease Control and Prevention.Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs -worldwide,2000-2004[J].Morb Mortal Wkly Ren,2006,55(11):301-305.
[9] WHO.2016 Global tuberculosis control.[DB/OL].Report.2016[R].WHO/HTM/TB /2016.https://aidsdatahub.org/global-tuberculosis-report-2016-who-2016
[10] Shen YZ,Lu HZ.The status of diagnosis and treatment for tuberculosis patients complicated with acquired immunodeficiency syndrome[J].Chinese J Pract Int Med,2015,35(8):671-674.
[11] Shen YZ,Zhang XY.Anti tuberculosis treatment for patients with AIDS coinfection with tuberculosis [J].Shanghai Med Pharm J ,2009,30(1):8-10.
[12] 中华人民共和国国家卫生健康委员会.艾滋病和艾滋病病毒感染诊断标准(WS 293-2008)[M].北京:人民卫生出版社.2008,6-9.
[13] 中围防痨协会基础专业委员会.结核病诊断实验室检验规程[M].北京:中围教育文化出版社.2006,46-52.
[14] 唐柳生,蒙志好,陈敬捷,等.艾滋病患者合并分枝杆菌感染及其耐药性分析[J].国际病毒学杂志,2016,23(5):336-338.
[15] 李世立,唐柳生,陈敬捷.艾滋病患者淋巴结结核分枝杆菌培养及耐药情况分析[J].国际检验医学杂志,2015,36(2):223-224.
[16] 刘俊,金永梅,等.合并艾滋病的结核病患者血液结核分枝杆菌培养阳性率影响因素的分析[J].临床肺科杂志,2018,23(7):1175-1178.
[17] Kendall BA,Winthrop KL.Update on the epidemiology of pulmonary nontuberculous mycobacterial infections[J] .Semin Respir Crit Care Med,20l3,34(1):87-94.
[18] Lan R,Yang C,Lan L,et al.Mycobacterium tuberculosis and non-tuberculous mycobacteria isolates from HIV-infected patients in Guangxi,China[J].Int J Tuberc Lung Dis,2011,15(12):1669-1675.
[19] 宋炜,刘莉,卢洪洲.艾滋病合并分枝杆菌感染患者分枝杆菌菌种鉴定[J].浙江大学学报(医学版),2016,45(3):243-248.
[20] 刘修武,范厚翠,葛成群,等.艾滋病患者非结核分枝杆菌感染的临床分析[J].中华医院感染学杂志,2016,26(10):2239-2241.
[21] Khatter S,Singh UB,Arora J,et al.Mycobacterial infections in human immunodeficiency virus seropositive patients:role of non-tuberculous mycobacteria[J].Indian J Tuberc,2008,55(1):28.
[22] 徐园红,崔振玲,胡忠义,等.四川地区200例随机临床分枝杆菌分离株耐药状况的分析研究[J].中华微生物学和免疫学杂志,2012,32(6):555-560.
[23] 邓西子,唐小平,雷杰,等.广州地区艾滋病患者合并感染分枝杆菌菌种的分布特征[J].中华传染病杂志,2015,33(6):331-334.
[24] 医学会结核病学分会,非结核分枝杆菌病实验室诊断专家共识编写组.非结核分枝杆菌病实验室诊断专家共识[J] .中华结核和呼吸杂志,2016,39(6):438-443.
[25] 王黎霞,成诗明,陈明亭.2010 年全国第五次结核病流行病学抽样调查报告[J].中国防痨杂志,2012,34(8):485-508.
[26] 刘敏,李奇穗,谭顺,等.艾滋病合并结核病患者结核分枝杆菌原发耐药的回顾性研究[J].中华传染病杂志,2017,35(5):278-281.
[2] Day JH,Grant AD,Fielding KL,et al.Does tuberculosis increase HIV load?[J].J Infect Dis,2004,190(9):1677-1684.
[3] Lawn SD,Badri M,Wood R.Tuberculosis among HIV-infected patients receiving HAART:long term incidence and risk factors in a South African cohort[J].AIDS,2005,19(18):2109-2116.
[4] Lopez-Gatell H,Cole SR,Margolick JB,et al.Effect of tuberculosis on the survival of HIV-infected men in a country with low tuberculosis incidence [J].AIDS,2008,22(14):1869-1873.
[5] The American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC).Targeted tuberculin testing and treatment of latent tuberculosis infection [J].MMWR Recomm Rep,2000,49(RR-6):1-51.
[6] Horsburgh CR Jr.Priorities for the treatment of latent tuberculosis infection in the United States[J].N Engl J Med,2004,350(20):2060-2067.
[7] Atwal SS,Puranik S,Madhav RK,et al.High resolution computed tomography lung spectrum in symptomatic adult HIV-positive patients in South-East Asian nation [J].J Clin Diagn Res,2014,8(6):RC12-RC16.
[8] Centers for Disease Control and Prevention.Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs -worldwide,2000-2004[J].Morb Mortal Wkly Ren,2006,55(11):301-305.
[9] WHO.2016 Global tuberculosis control.[DB/OL].Report.2016[R].WHO/HTM/TB /2016.https://aidsdatahub.org/global-tuberculosis-report-2016-who-2016
[10] Shen YZ,Lu HZ.The status of diagnosis and treatment for tuberculosis patients complicated with acquired immunodeficiency syndrome[J].Chinese J Pract Int Med,2015,35(8):671-674.
[11] Shen YZ,Zhang XY.Anti tuberculosis treatment for patients with AIDS coinfection with tuberculosis [J].Shanghai Med Pharm J ,2009,30(1):8-10.
[12] 中华人民共和国国家卫生健康委员会.艾滋病和艾滋病病毒感染诊断标准(WS 293-2008)[M].北京:人民卫生出版社.2008,6-9.
[13] 中围防痨协会基础专业委员会.结核病诊断实验室检验规程[M].北京:中围教育文化出版社.2006,46-52.
[14] 唐柳生,蒙志好,陈敬捷,等.艾滋病患者合并分枝杆菌感染及其耐药性分析[J].国际病毒学杂志,2016,23(5):336-338.
[15] 李世立,唐柳生,陈敬捷.艾滋病患者淋巴结结核分枝杆菌培养及耐药情况分析[J].国际检验医学杂志,2015,36(2):223-224.
[16] 刘俊,金永梅,等.合并艾滋病的结核病患者血液结核分枝杆菌培养阳性率影响因素的分析[J].临床肺科杂志,2018,23(7):1175-1178.
[17] Kendall BA,Winthrop KL.Update on the epidemiology of pulmonary nontuberculous mycobacterial infections[J] .Semin Respir Crit Care Med,20l3,34(1):87-94.
[18] Lan R,Yang C,Lan L,et al.Mycobacterium tuberculosis and non-tuberculous mycobacteria isolates from HIV-infected patients in Guangxi,China[J].Int J Tuberc Lung Dis,2011,15(12):1669-1675.
[19] 宋炜,刘莉,卢洪洲.艾滋病合并分枝杆菌感染患者分枝杆菌菌种鉴定[J].浙江大学学报(医学版),2016,45(3):243-248.
[20] 刘修武,范厚翠,葛成群,等.艾滋病患者非结核分枝杆菌感染的临床分析[J].中华医院感染学杂志,2016,26(10):2239-2241.
[21] Khatter S,Singh UB,Arora J,et al.Mycobacterial infections in human immunodeficiency virus seropositive patients:role of non-tuberculous mycobacteria[J].Indian J Tuberc,2008,55(1):28.
[22] 徐园红,崔振玲,胡忠义,等.四川地区200例随机临床分枝杆菌分离株耐药状况的分析研究[J].中华微生物学和免疫学杂志,2012,32(6):555-560.
[23] 邓西子,唐小平,雷杰,等.广州地区艾滋病患者合并感染分枝杆菌菌种的分布特征[J].中华传染病杂志,2015,33(6):331-334.
[24] 医学会结核病学分会,非结核分枝杆菌病实验室诊断专家共识编写组.非结核分枝杆菌病实验室诊断专家共识[J] .中华结核和呼吸杂志,2016,39(6):438-443.
[25] 王黎霞,成诗明,陈明亭.2010 年全国第五次结核病流行病学抽样调查报告[J].中国防痨杂志,2012,34(8):485-508.
[26] 刘敏,李奇穗,谭顺,等.艾滋病合并结核病患者结核分枝杆菌原发耐药的回顾性研究[J].中华传染病杂志,2017,35(5):278-281.